Heparinase is an enzyme which cleaves certain glycosidic linkages in heparin, a sulfated mucopolysaccharide having the major repeating unit: -4)-2-deoxy-2-sulfamino-.alpha.-D-glucopyranose-o-sulfate-(1-4)-.alpha.-L- idopyranosyluronic acid-2-sulfate-(1-. The products of this enzyme activity are chain-shortened fragments of heparin. Heparinase also cleaves heparitin (otherwise known as heparin monosulfate or heparin sulfate), a sulfated mucopolysaccharide having a chemical structure similar to that of heparin, producing chain-shortened fragments of heparitin.
The substrate, heparin, is widely used as an anticoagulant drug and consequently heparinase has numerous applications in the study of heparin structure, investigation of the blood coagulation mechanism, and in bioassays for detection of heparin in body tissues and fluids. Heparinase also has use in the preparation of low molecular weight heparin fragments which have potential therapeutic value as anti-thrombotic or anti-tumour agents.
Heparinase derived from microorganisms of the genus Bacillus is new. Previously, enzymes capable of degrading heparin have been detected only in cultures of Flavobacterium heparium, Flavobacterium sp., Bacteroides sp., Bacteroides heparinolyticus, Peptostriptococcus and Eubacterium. These heparinases are disclosed in Journal of Biochemistry [Vol. 233, p. 853 (1956)]; Experientia [Vol. 41, p. 1541 (1985)]; Matsumoto Dental School Journal (Japan) [Vol. 8, p. 15 (1982)]; Journal of Applied and Environmental Microbiology [Vol. 46, p. 1252 (1983)]; Journal of Clinical Microbiology [vol. 26, p. 1070 (1988)]; Journal of the South African Veterinary Association [Vol. 53, p. 214 (1982)].
The conventional heparinases all have one or more disadvantages, such as high cost of enzyme production and recovery, and low stability during purification, storage and use, which limit their practical use. At present, only the heparinase from Flavobacterium heparinum is commercially available.